In 1976, Clapton was the centre of controversy and accusations of racism, when he spoke out against increasing immigration during a concert in Birmingham. He commented that England had "...become overcrowded...that England sells itself as the "land of milk and honey" only to turn around and stick its invited immigrants into low paying labour jobs, living in substandard conditions..." Clapton also voiced his support of controversial political candidate Enoch Powell, making references to "a black colony." These comments (along with equally controversial remarks and actions by other artists, such as David Bowie and Siouxsie Sioux) led to the creation of the Rock Against Racism movement in the UK.

Clapton has performed songs by myriad artists, most notably Robert Johnson and J.J. Cale. Other artists Clapton has covered include Bob Marley and Bob Dylan. He cites Freddie King, B.B. King, Albert King, Buddy Guy, Hubert Sumlin and primarily Robert Johnson as major influences on his guitar playing, stating in the liner notes of his Robert Johnson tribute album Me and Mr. Johnson "It is a remarkable thing to have been driven and influenced all of my life by the work of one man... I accept that it has always been the keystone of my musical foundation... I am talking of course about Robert Johnson."

With the Yardbirds, Clapton played a Fender Telecaster and a cherry-red Gibson ES-335. He became exclusively a Gibson player for a period beginning in mid-1965, when he purchased a used Gibson Les Paul Sunburst Standard guitar from a local guitar store in London. It is not known of the exact year of the guitar, but Clapton commented on the slim profile of the neck, which would indicate it as a 1960 model. He would later use the guitar on the 1966 album with John Mayall & the Bluesbreakers and was largely responsible for Gibson's reintroduction of the original Les Paul body style in 1968 after it had been replaced by the Gibson SG.